I-Pharmacogenomics iyavakala — ngoko kutheni iinkampani zamachiza zingayisebenzisi ngokwenene?

I-Pharmacogenomics (PGx) ifikelele kwimpikiswano engaqhelekanga. Ubungqina besayensi buqolile, inzuzo yayo kwezonyango (nakwezoqoqosho) ayinakuphikiswa, kanti ke ukwamkelwa kwayo kusahlala kucotha, kucalucalwe, kwaye kungalingani.
 

Ingakumbi kuvavanyo lwezonyango, uprofayilisho lwe-pharmacogenomic alusetyenziswa kangako. Ukuhlola kwi-ClinicalTrials.gov kufumene kuphela iimvavanyo zokungenelela ezinxulumene ne-PGx ezingama-619 kwizibalo eziyi-350,728 zizonke (~0.18%), kwaye ngaphantsi kwesiqingatha zazo zicacise ngokucacileyo ukuba zeziphi iijini ezazifundwa, nangona i-PGx kuvavanyo inokwenza izinto ezininzi ezisebenzisekayo:
 

Umyalezo ocace gca wokusebenza: ukwahluka okuncinci -> ibali elicace gca lomphenduli/ongaphenduliyo Iziganeko
zokhuseleko ezimbalwa: ukuchonga iijenotypes ezisengozini enkulu kwangethuba -> iziphumo ezibi ezibangelwa ngamachiza (ADRs) ezimbalwa
ezinokuphetshwa Ukunqaba kokuphazamiseka kovavanyo: ukunqaba kokunqunyanyiswa, amayeza okusindisa ambalwa, iimeko ezingxamisekileyo ezimbalwa ("fire drills")
Isicwangciso sedosi esingcono kwisigaba sokuqala: i-PGx inceda ukucacisa iziphumo ezingaqhelekanga ze-PK/PD phambi kokuba zibe ngamangalo angalindelekanga
obutyhefu obuthintela idosi Amabali aqinileyo ekugqibeleni: amaqelana angaphakathi achazwe kwangaphambili -> isicwangciso seleyibhile esinokukhuselwa ngakumbi kubahlawuli
 

Kwiqela elininzi lophuhliso, i-PGx isenokubonakala njengento eyongeza ubunzima ngaphandle kokunciphisa umngcipheko ngokucacileyo: iimvavanyo ezininzi, ulungelelwaniso olungakumbi, imibuzo emininzi yolawulo, izinto ezininzi ezinokonakala. Xa amaxesha emfutshane kwaye ukusilela kubiza kakhulu, isimo sengqondo siba kukwenza izinto zibe lula, hayi ukwazisa enye into etshintshayo, nokuba loo nto ibalulekile ngokwezonyango. Yiloo nto kanye eyenza i-PGx ibe nobunzima bokutshintsha isuka ekubeni "ngumbono omhle" iye ekubeni "sisiseko esisisigxina" kuvavanyo lwezonyango.
Iingxelo zamava eengcali zonyango zikwaphawula ukuba iiphaneli zePGx zorhwebo zinokuphoswa ziijini eziphambili ezinokuthathyathwa amanyathelo ngokwezikhokelo ze-CPIC/FDA/DPWG, ngelixa zibandakanya iintlobo ezinebango eliphantsi lobungqina, nto leyo eyenza kube nzima ukwazi ukuba zeziphi iziphumo eziluncedo ngokwenene ekusebenzeni. Nokuba ijini efanelekileyo iyabandakanywa, iiphaneli zinokungasoloko zifumana zonke iialeli ezinokuthathyathwa amanyathelo ngokwezonyango (ezinjengeentlobo zokuguqulwa kwenani leekopi okanye izakhiwo ezixutyiweyo), nto leyo enokukhokelela ekubekweni ngokungachanekanga kweendidi zeemetabolizer kubathathi-nxaxheba.
 

Nokuba kuvavanyo lwe-PGx luyasetyenziswa, kufuneka lungene kwizikhokelo zexesha eliqinileyo lovavanyo: iinkqubo ezifana ne-PREPARE zifuna iziphumo zibuyiswe kwisithuba esimalunga neentsuku ezisi-7 ukuze zihlale zibalulekile kwezonyango, kwaye kwiimeko zokwenyani ukusebenzisa i-PGx kubandakanya yonke into ukusuka kukhetho lwejenes kwaye ukuguqulelwa kwe-phenotype ukuya ekunikezeleni ingxelo, i-CDS logic, kunye nokudityaniswa kwe-EHR kumaqela amaninzi. Enyanisweni, ukuguqula idatha yokulandelelana kwejenom ibe ziiphenotypes ezihambelana nezikhokelo kudla ngokuxhomekeka kwiipayiplayini ezikhethekileyo ze-bioinformatics kunye neziseko ezingundoqo zalapho, nto leyo ebangela ukulibaziseka, imingeni yokutolika, kunye nokwahluka-hluka kwiindawo ezahlukeneyo, apho oogqirha bahlala bekhankanya ukunqongophala kwexesha kunye nokutolikwa kweziphumo okunzima njengezithintelo eziphambili.
 

Okumangalisayo kukuba eyona ngxoxo inamandla ye-pharmacogenomics sele yenziwe. Uphando lwe-PREPARE lubonise ukuba i-PGx yokuqola (pre-emptive) inciphisa iziphumo ezibi zamachiza ezibalulekileyo ngokwezonyango malunga nama-30%. Oko akuncinci. Lolo hlobo lobungakanani bentsebenzo iinkampani zamachiza (pharma) zidla ngokulubhiyozela.
 

Kodwa uphando lwe-PREPARE lukwabonise ngokuzolileyo isizathu sokuba i-PGx ingekazaziwa ngokubanzi: i-genotyping edityaniswe kwindawo enye, amaxesha okufumana iziphumo athatha iintsuku ezininzi, ulungelelwaniso olunzima, umthwalo wokucubungula idatha, kunye neepaneli ezazange zayilelwa iimvavanyo zehlabathi jikelele ezihamba ngesantya esiphezulu.
Ngamanye amazwi, ibhayoloji yayisebenza. Ulungiselelo lwezinto lwalungasebenzi.
Kulapho ke i-DNA ME ingena khona.
Kwa-DNA ME, sisisebenzisa isisombululo se-software esisebenza kakuhle nesilula esisekelwe kwi-nanopore sequencing ukujongana ne-pharmacogenomics, kuba lo mdibaniso ekugqibeleni wenza i-PGx ihambelane nendlela iimvavanyo ezisebenza ngayo ngokwenene.
 

I-Nanopore sequencing ikuvumela ukuba uvelise idatha yezofuzo kufutshane nendawo yovavanyo endaweni yokuthumela iisampulu kwilabhoratri emanyeneyo. Okubaluleke ngakumbi, i-long-read sequencing ichaza i-pharmacogenes ezibaluleke kakhulu (njenge-CYP2D6) ngaphandle kokuqikelela nokuhlelwa gwenxa okukhathaza i-short-read yesiqhelo.

Iiphaneli. Kodwa ukulandelelana yisiqingatha nje sebali. Okubalulekileyo ngokwenene kukwenzeka emva kokuba idatha iveliswe.
 

I-DNA ME iguqula iifundi ezikrwada zibe ziziphumo zefarmakojinomiki ezisemgangathweni ezifundeka ngumatshini nezilungele iimvavanyo, kungekho mfuneko yeengcali ze-bioinformatics ukufikelela kwiziphumo zokulandelela. Le datha ingangena ngqo kukuqwalaselwa kokhuseleko, kwimithetho yokunyusa idosi, okanye kwingqiqo yovavanyo oluziqhelanisayo. Uhlalutyo lunokuqhutywa nakwi-laptop eqhelekileyo; akukho mfuneko yee-GPU okanye izixhobo zekhompyutha ezibizayo, kwaye kungekho kufakwa okanye ukuthunyelwa kwedatha yemfuzo yomthathi-nxaxheba ebuthathaka.
 

Indlela yokusebenza ye-DNA ME esekelwe kwi-nanopore inokufumanisa i-CpG methylation kunye ne-allele-specific methylation ngokuthe ngqo kuloo nkqubo inye yokulandelela, yongeza umaleko ongasebenziyo kuprofayilisho lwe-pharmacogenomic ngaphandle kweemvavanyo ezongezelelweyo okanye ulungiso olulandelayo. Oku kwenza ukuba kubekho ukuchongwa kwabathathi-nxaxheba abane-metabolism yabo yokwenyani enokwahluka kwi-genotype yabo eqikelelweyo ngenxa yolawulo lwe-epigenetic lwee-pharmacogenes, kunceda ekunciphiseni iziganeko ezingaqhelekanga zokuchanabeka kunye nokuphucula udidi lwe-metabolizer ngaphakathi kwenkqubo enye elula.
 

Ngomzuzu i-PGx iba yeyokukhawuleza, efikelelekayo, kwaye ingabonakali ekusebenzeni (ifakwe ngendlela efanayo neyokufakelwa kwe-PK sampling okanye iilabhu zokhuseleko), ishishini lamachiza liyayeka ukubuza ukuba kufanelekile na ukuyenza. Umbuzo uba ngowokuba kutheni bengawamkela umngcipheko wokungayenzi.

Ukuba ukhe wazama ukudibanisa i-PGx kuvavanyo, yintoni eyona nto ibiyithintelayo: iindleko, ixesha lokugqiba, imisebenzi, okanye inkxaso yangaphakathi?

Sinomdla wokwazi ukuba ngawaphi amaqela afumanisa izinto ezahlukeneyo kwindawo yokusebenza.

(Kwaye ukuba ufuna iphaneli elungele uvavanyo + inkqubo ye-nanopore ekulula ukuyisebenzisa elungiselelwe isixhobo sakho, sithumelele umyalezo ku-DNA ME kwaye siza kuyakha nawe.)